Composition and method of treating a sore throat

ABSTRACT

A composition comprising an antacid, and a local, topical anesthetic. The composition is used to relieve pain or discomfort associated with a sore throat, and therefore, the invention is also directed to a method of alleviating the pain or discomfort associated with a sore throat comprising instructing a human to orally administer the composition.

FIELD OF THE INVENTION

The invention relates to a composition comprising an antacid and alocal, topical anesthetic. As the composition dissolves or disintegratesin the mouth the antacid and local, topical anesthetic is released fromthe composition thereby relieving the discomfort often associated with asore throat.

BACKGROUND OF THE INVENTION

The delivery of drugs through the buccal mucosa is a very well known andconvenient way of administering a number of active ingredients foreither local or systemic action. Chewable tablets, lozenges and othersimilar oral dosage forms have been present on the market for manyyears. These galenical forms often consist of a soluble diluent, such assugar, lactose, mannitol or sorbitol, and a binder. Lubricants, flavors,sweetening agents, or taste correctors are also often present in thesedosage forms. These forms dissolve relatively rapidly once in the mouth,within either a few seconds or up to 10 minutes, and deliver bothsoluble and insoluble active ingredients to the buccal cavity.

SUMMARY OF THE INVENTION

The invention is directed to a composition comprising an antacid, and alocal, topical anesthetic. The composition is used to relieve pain ordiscomfort associated with a sore throat, and therefore, the inventionis also directed to a method of alleviating the pain or discomfortassociated with a sore throat comprising instructing a human to orallyadminister a composition comprising an antacid and a local, topicalanesthetic.

DETAILED DESCRIPTION OF THE INVENTION

A sore throat can develop for a number of reasons including a viral orbacterial infection, or a common or seasonal allergy. Often associatedwith an infection, common or seasonal allergy is some degree of nasal orsinus congestion. This congestion is typically referred to as post-nasaldrip, in which mucous originating on the surface of the nasal mucosa orthe sinus mucosa drains onto the upper esophagus. The accumulation ofnasal mucosa in the upper esophagus also stimulates the swallowingreflex often associated with a sore throat. The swallowing reflextransports the acidic mucous into relatively constant contact with theregion of the throat. The acidic nature of the mucous from the sinusmucosa or nasal mucosa erodes the epithelial tissue of the throatthereby exposing the underlying tissue to the acidic mucous. The nerveendings in the underlying tissue in contact with the acidic mucosa causewhat we identify as the discomfort or pain associated with a sorethroat. The more inflamed the nasal mucosa or the sinus mucosa, thegreater the production of the acidic mucous, the greater the erosion andthe greater the severity of the pain and discomfort associated with thesore throat.

The composition comprises an antacid to neutralize in-part the acidicnature of the mucous, which in turn, helps to minimize the amount oferosion and/or subsequent exposure of the underlying tissue and exposednerve endings to an acidic environment. The relatively slow release ofthe antacid from the composition helps to counteract the acidic mucosafrom the sinus that is constantly draining into the upper esophagus andbeing swallowed. The composition provides a controlled antacid deliveryform for the administration of an antacid. As the controlled dosageform, e.g., a lozenge, slowly dissolves in the mouth, a sustainedrelease of the antacid is achieved which neutralizes the acidicenvironment in the throat region caused by the acidic mucosa.Surprisingly, only a small amount of antacid is needed to adjust the pHof the throat region and provide relief for tissues inflamed by theacidic mucosa.

The antacid can be one or more of antacid agents such as sodium,calcium, magnesium or aluminum salts that are commonly used toneutralize gastric fluids. Exemplary antacids are sodium bicarbonate,sodium citrate, calcium carbonate, calcium phosphate, magnesium oxide,magnesium hydroxide, magnesium carbonate, magnesium trisilicate,aluminum carbonate and aluminum hydroxide. Other suitable antacidsinclude dihydroxy aluminum sodium carbonate, dihydroxy aluminumaminoacetate and magnesium hydroxy aluminates. Various otherco-precipitates of aluminum hydroxides or carbonates with magnesiumhydroxides or carbonates, hexitols, aminoacetic acid or the like canalso be used.

The process of neutralizing the acid mucous brings relief to thediscomfort associated with a sore throat. In many embodiments, theantacid composition includes a combination of magnesium and aluminumsalts, calcium and aluminum salts or magnesium and calcium salts. Theantacid is provided in a sufficient quantity to effect the acidneutralization of the throat region over a selected period, for example,15 to 60 minutes. To that end each lozenge has from 10 to 40 meq. ofantacid, preferably from 20 to 30 meq of antacid.

The composition also contains one or more local, topical anestheticagents. The local, topical anesthetic agents also help to alleviate thepain or discomfort often associated with a sore throat, particularly asthe throat undergoes a swallowing-type action. Exemplary local, topicalanesthetic agents include lidocaine, benzocaine, tetracaine, dyclonineand mixtures thereof. Benzocaine and tetracaine are two of the preferredlocal, topical anesthetic agents used in the composition.

The composition can also contain one or more sweeteners to make it morepalatable. For example, any sugar or sugar-free sweetener, e.g.maltitol, xylitol, sorbitol, mannitol, lactose, dextrose, saccharose orfructose, or any mixture thereof, e.g. a mixture of xylitol andsorbitol, such as Xylisorb® can be used in the composition. Some of themore preferred sweeteners include maltitol, xylitol, mannitol, dextrose,sorbitol, fructose, or any mixture thereof. The sweeteners can bepresent in an amount of from 30 to 95 wt. %, from 50 to 90 wt. % andfrom 70 to 90 wt. % of the total composition.

The composition is formulated as a dosage form that slowly dissolves ordisintegrates in the mouth. As a result, the composition will typicallycontain a relative large amount of a sweetener. Suitable good tastingsweeteners include the sugar alcohols mannitol, sorbitol and xylitol.Sugar alcohols are preferred because they provide compositions such as alozenge or a chewing gum that is “sugarless”. Mannitol is one of thepreferred sugar alcohols because it is less soluble than sorbitol. Also,mannitol provides a slightly sweet product with a particularlyrefreshing or cooling affect.

If the composition includes a sugar alcohol, it may be necessary to addan artificial sweetener to provide a composition with an acceptabletaste. Although mannitol is a preferred sweetener, it may be substitutedby or used in combination with other sugar alcohols. If a candy likelozenge is desired, sucrose, dextrose or the like can be used in placeof the sugar alcohol. Because these sugars are more soluble thanmannitol, the amount of the swelling agent or matrix forming agentsshould be increased to provide a composition in a dosage form that willrelease the antacid and local, topical anesthetic over a selected timeperiod, e.g., 10 to 30 minutes.

One or more matrix-forming agents that are capable of forming a matrixthat can be present in the composition include, for example,polyacrylates, which means homo- or co-polymers of alkyl esters,especially methyl and ethyl esters but also e.g. substituted alkylesters such as dimethylaminoethyl esters, of acrylic acid and/ormethacrylic acid, e.g. Eudragit® products such as Eudragit® S, Eudragit®NE, Eudragit® E or Eudragit® L of Roehm Pharma GmbH, Darmstadt(Germany). Other matrix-forming agents include e.g. ethyl cellulose,e.g. Aquacoat® products such as Aquacoat® ECD 30 of FMC Corp.,Philadelphia (USA); polyvinylchloride, cellulose acetate, celluloseacetate phthalate or shellac. Again, mixtures of more than one of thematrix-forming agent can also be present in the composition. Thematrix-forming agent is typically present in an amount of from 0.5 to 30wt. %, from 0.5 to 24 wt. % and from 3 to 10 wt. %, based on the totalcomposition.

Some of the more preferred matrix-forming agents include polyacrylates,and especially such polyacrylates which are in the form of an aqueousdispersion, for example Eudragit® NE 30D.

In the manufacture of the composition, the matrix-forming agent can beapplied as an aqueous dispersion (pseudolatex), as a non-aqueousdispersion (using an organic solvent) or in solid form. Thematrix-forming agents are intimately mixed with the other components ofthe composition.

The composition can also contain one or more swellable polymers selectedfrom a naturally occurring or synthetically obtained swellable polymerthat is pharmaceutically acceptable. Examples of some useful swellablepolymers include xanthan gum, guar gum, alginic acid or a salt thereof,such as sodium alginate, pectins, polyvinyl alcohol, polysaccharides andswellable cellulose derivatives such as sodium or calciumcarboxymethylcellulose. Again, a mixture of more than one of theswellable polymers can be present in the composition. The one or moreswellable polymers can be present in an amount of from 0.5 to 30 wt. %,from 0.5 to 24 wt. % and from 3 up to 10 wt. %, of the totalcomposition.

Some of the more preferred swellable polymers include xanthan gum, guargum, alginic acid or a salt thereof, such as sodium alginate, andswellable cellulose derivatives such as sodium or calciumcarboxymethylcellulose, hydroxypropylmethylcellulose,hydroxyethylcellulose or hydroxypropylcellulose. One of the morepreferred swellable polymers is xanthan gum.

A water insoluble lipid material can also be present in the compositionas a swelling agent. This lipid material can be a hydrophobic metal saltof a fatty acid such as stearic acid, palmetic acid, oleic acid andlauric acid. Applicable metals for formation of the above salts includemagnesium, calcium and aluminum. Of these materials, magnesium andcalcium stearate are preferred.

As the composition dissolves or disintegrates in the mouth, e.g., by thesucking of a lozenge, the swellable polymers swell on the surface of thelozenge. Small pieces of the swellable polymer erode from the surface ofthe lozenge together with the matrix-forming agent. The rate at whichthe lozenge dissolves in the mouth will depend on the formulation. Amore slowly dissolving lozenge is obtained, if the amount of thematrix-forming agent, e.g. a polyacrylate dispersion, and/or the amountof the swellable polymer, e.g. xanthane gum, is increased.

The composition can also contain an anti-inflammatory agent. Oneparticular anti-inflammatory agent present in the composition isflurbiprofen [2-(2-fluoro-4-biphenylyl)propionic]acid, which is anon-steroidal anti-inflammatory agent with known analgesic activity. Theflurbiprofen molecule exists in two enantiomeric forms and the termflurbiprofen as used herein includes the individual enantiomers andmixtures thereof in any proportion including a 1:1 mixture which isherein referred to as racemic flurbiprofen. Flurbiprofen can exist inthe form of pharmaceutically acceptable salts or in the form ofderivatives such as esters and such salts or esters are embraced by theterm “flurbiprofen” as used herein.

The flurbiprofen is present in the composition in an amount from 2.5 to20 mg preferably 5 to 12.5 mg. Where a pharmaceutically acceptable saltof flurbiprofen is used, the amount of the salt used should be such asto provide the desired amount of flurbiprofen. Suitable salts includethe alkali metal salts eg the sodium salt or amino acid salts eg thelysine, arginine or meglumine salts of flurbiprofen.

The compositions can also contain one or more auxiliary agents known inthe art and include lubricants, flavors, aromas, colorants, diluents,preservatives, glidants, e.g. colloidal silicium dioxide, and the like.

The composition can be provided as a lozenge, which can be prepared byseveral known methods including:

(1) a traditional wet granulation process incorporating all ingredients,and subsequent compression, or

(2) a two stage process consisting of a granulation stage of only someof the ingredients, which is followed by the addition of the otheringredients, e.g. the active substance, in the external phase (seeExamples 1, 2, 3 and 5), and subsequent compression, or

(3) a direct compression process without a granulation stage (seeExample 4).

Example 1 Composition (for 1000 Lozenges)

Benzocaine 20.0 g; Maltitol 880.0 g; Sodium bicarbonate 20.0 g;Polyacrylate dispersion 30% 50.0 g (dry mass); Xanthane gum 40.0 g;Colloidal anhydrous silica 15.0 g; and Magnesium stearate 20.0 g.

To a fluid bed mix containing the maltitol, sodium carbonate and ⅔ ofthe colloidal anhydrous silica is added the polyacrylate dispersionusing a contra-current fluid bed granulation. The addition of thebenzocaine, xanthane gum, the remaining ⅓ of the colloidal anhydroussilica and the magnesium stearate follows. The mixture is compressed toproduce 15 mm biconvex round lozenges with a mass of about 1045 mg each.

Example 2 Composition (for 1000 Lozenges)

Benzocaine 50.0 g; Maltitol 880.0 g; Sodium carbonate anhydrous 40.0 g;Polyacrylate dispersion 30% 70.0 g (dry mass); Xanthane gum 60.0 g;Colloidal anhydrous silica 15.0 g; Peppermint 30.0 g; Levomenthol 3.0 g;Saccharine sodium 5.0 g; and Magnesium stearate 20.0 g.

To a fluid bed mix containing the maltitol, sodium carbonate anhydrous,and ⅔ of the colloidal anhydrous silica is added the polyacrylatedispersion using a contra-current fluid bed granulation. The addition ofthe benzocaine, xanthane gum, the remaining ⅓ of the colloidal anhydroussilica, the levomenthol, peppermint, saccharine sodium and the magnesiumstearate follows. The mixture is compressed to produce 15 mm biconvexround lozenges with a mass of about 1173 mg each.

Example 3 Composition (for 1000 Lozenges)

Benzocaine 50.0 g; Xylitol 880.0 g; Sodium carbonate anhydrous 40.0 g;Polyacrylate dispersion 30% 50.0 g (dry mass); Xanthane gum 40.0 g;Colloidal anhydrous silica 15.0 g; Cinnamon flavour 15.0 g; Saccharinesodium 5.0 g; and Magnesium stearate 20.0 g.

To a fluid bed mix containing the maltitol, sodium carbonate anhydrous,and ⅔ of the colloidal anhydrous silica is added the polyacrylatedispersion using a contra-current fluid bed granulation. The addition ofthe benzocaine, xanthane gum, the remaining ⅓ of colloidal anhydroussilica, the levomenthol, peppermint, saccharine sodium and the magnesiumstearate follows. The mixture is compressed to produce 15 mm biconvexround lozenges with a mass of about 1115 mg each.

Example 4 Composition (for 1000 Lozenges)

Benzocaine 50.0 g; Xylisorb® (a mixture of xylitol and sorbitol) 850.0g; Sodium carbonate anhydrous 40.0 g; Eudragit® S-100 100.0 g; Xanthanegum 40.0 g; Colloidal anhydrous silica 5.0 g; Peppermint 30.0 g;Levomenthol 3.0 g; Saccharine sodium 5.0 g; and Magnesium stearate 20.0g.

Mix all the ingredients together, except for the magnesium stearate, andscreen through a Frewitt fitted with a screen of 0.63 mm aperture size.Add the magnesium stearate and mix for 5 minutes. The mixture iscompressed to produce 15 mm biconvex round lozenges with a mass of about11143 mg each.

Example 5 Composition (for 1000 Lozenges)

Benzocaine 50.0 g; Maltitol 880.0 g; Sodium carbonate 10.0 g; Sodiumbicarbonate 20.0 g; Polyacrylate dispersion 30% 50.0 g (dry mass);Xanthane gum 40.0 g; Colloidal anhydrous silica 15.0 g; Levomenthol 3.0g; Peppermint oil 5.0 g; Aspartame 10.0 g; and Magnesium stearate 20.0 g

To a fluid bed mix containing the maltitol, sodium carbonate, sodiumbicarbonate and ⅔ of the colloidal anhydrous silica is added thepolyacrylate dispersion using a contra-current fluid bed granulation.The addition of the benzocaine, xanthane gum, the remaining ⅓ of thecolloidal anhydrous silica, the magnesium stearate, levomenthol,peppermint oil, and aspartame follows. The mixture is compressed toproduce 15 mm biconvex round lozenges with a mass of about 1103 mg.

EXAMPLES 6

A wet granulation having the composition shown in Table 1 is prepared asfollows: The mannitol, aluminum hydroxide-magnesium carbonatecoprecipitate and magnesium carbonate are mixed in a twin shell blenderfor 5 minutes. The gelatin is dissolved in water and heated to 60° C.The gelatin solution is mixed with the above-described blend in aSimpson mixmuller to form a wet granulation. The wet granulation isspread on a tray and dried at 60° C. for 8 hours. The dried granulationis then passed through a Erweka granulator to reduce the dried materialto an 18 mesh or finer particle size. This dried material is called theraw granulation.

TABLE 1 Mannitol Powder 48.17 wt. % Aluminum Hydroxide-MagnesiumCarbonate Coprecipitate 25.74 wt. % Magnesium Carbonate 16.79 wt. %Benzocaine 5.0 wt. % Gelatin Solution, 10% weight/weight 4.33 wt. %.

Lozenges having the composition shown in Table 2 are prepared asfollows. The raw granulation, sodium carboxymethyl cellulose, calciumstearate, talc and flavorant are mixed for 15 minutes in a twin shellblender. This mixture is then made into lozenges on a Stokes RD-3 tabletpress with ⅝ in. die and deep concave punches at a pressure of 7 tons.The lozenges will have 18 meq. of antacid neutralizing capacity.

TABLE 2 Raw Granulation 91.33 wt. % Sodium Carboxymethyl Cellulose 5.00wt. % Calcium Stearate 1.00 wt. % Talc 1.00 wt. % Flavorant 1.67 wt. %Benzocaine 5.0 wt. %

Example 7

A raw granulation having the composition shown in Table 3 is preparedaccording to the procedure of Example 6 except that calcium carbonate isused as the antacid component and starch paste is used as the auxiliarybinder. The wet granulation is dried at 60° C. for 24 hours. Lozengeshaving the composition are prepared following the procedure of Example 6with the exception that the raw granulation mix of Table 3 is used.

TABLE 3 Mannitol Powder 19.63% Calcium Carbonate 71.75 wt. % Benzocaine5.0 wt. % Starch Paste, 10% weight/weight 3.92%

Example 8

A raw granulation having the composition shown in Table 4 is preparedaccording to the procedure of Example 6.

TABLE 4 Mannitol Powder 53.87 wt. % Aluminum Hydroxide-MagnesiumCarbonate Coprecipitate 9.43 wt. % Magnesium Carbonate 13.47 wt. %Calcium Carbonate 11.52 wt. % Benzocaine 2.0 wt. % Starch Paste, 10%weight/weight 4.71 wt. %

Lozenges having the composition shown in Table 5 were prepared followingthe procedure of Example 6. The lozenges are hard, slow dissolving andwill have 24 meq. of antacid neutralizing capacity.

TABLE 5 Raw Granulation 93.34 wt. % Sodium Carboxymethyl Cellulose 3.00wt. % Calcium Stearate 1.00 wt. % Talc 1.00 wt. % Flavorant 1.66 wt. %Benzocaine 2.0 wt. %

Example 9

A raw granulation having the composition shown in Table 6 is preparedaccording to the procedure of Example 6.

TABLE 6 Mannitol Powder 31.53 wt. % Sorbitol Solution, 10% weight/weight4.74 wt. % Aluminum Hydroxide-Magnesium Carbonate Coprecipitate 14.34wt. % Magnesium Hydroxide 40.37 wt. % Benzocaine 2.0 wt. % GelatinSolution, 15% weight/weight 7.12 wt. %

Lozenges having the composition shown in Table 7 are prepared followingthe procedure of Example 6. The lozenges will have 33 meq. of acidneutralizing capacity.

TABLE 7 Raw Granulation 88.34 wt. % Sodium Carboxymethyl Cellulose 5.00wt. % Calcium Stearate 2.00 wt. % Talc 1.00 wt. % Flavorant 1.66 wt. %Benzocaine 2.0 wt. %

Example 10

A raw granulation having the composition shown in Table 8 is preparedaccording to the procedure of Example 9.

TABLE 8 Mannitol Powder 47.88 wt. % Sorbitol Solution, 10% weight/weight4.40 wt. % Aluminum Hydroxide-Magnesium Carbonate Coprecipitate 13.57wt. % Magnesium Carbonate 25.53 wt. % Benzocaine 2.0 wt. % GelatinSolution, 15% weight/weight 6.60 wt. %

Lozenges having the composition shown in Table 9 are prepared followingthe procedure of Example 6 except that xanthan gum is substituted forthe sodium carboxymethyl cellulose.

TABLE 9 Raw Granulation 91.59 wt. % Xanthan Gum 3.00 wt. % CalciumStearate 1.00 wt. % Talc 1.00 wt. % Flavorant 1.41 wt. % Benzocaine 2.0wt. %

1. A sore throat composition consisting essentially of mannitol powder,calcium carbonate, benzocaine, and starch paste.
 2. The sore throatcomposition of claim 1, wherein the calcium carbonate provides from 10to 40 meq. of antacid neutralizing capacity.
 3. The sore throatcomposition of claim 1, wherein the calcium carbonate provides from 20to 30 meq. of antacid neutralizing capacity.
 4. The sore throatcomposition of claim 1, wherein the benzocaine is present in an amountof from 0.5 wt. % to 20 wt. %.
 5. The sore throat composition of claim1, wherein the mannitol powder is present in an amount of from 30 wt. %to 95 wt. %.
 6. The sore throat composition of claim 1, in form of alozenge or chewing gum.
 7. A sore throat composition consistingessentially of mannitol powder, aluminum hydroxide-magnesium carbonatecoprecipitate, magnesium carbonate, calcium carbonate, benzocaine, andstarch paste.
 8. The sore throat composition of claim 7, wherein thealuminum hydroxide-magnesium carbonate coprecipitate, magnesiumcarbonate, and calcium carbonate provide from 10 to 40 meq. of antacidneutralizing capacity.
 9. The sore throat composition of claim 7,wherein the aluminum hydroxide-magnesium carbonate coprecipitate,magnesium carbonate, and calcium carbonate provide from 20 to 30 meq. ofantacid neutralizing capacity.
 10. The sore throat composition of claim7, wherein the benzocaine is present in an amount of from 0.5 wt. % to20 wt. %.
 11. The sore throat composition of claim 7, wherein themannitol powder is present in an amount of from 30 wt. % to 95 wt. %.12. The sore throat composition of claim 7, in form of a lozenge orchewing gum.
 13. A sore throat composition consisting essentially ofmannitol powder, calcium carbonate, benzocaine, starch paste, and anauxillary agent.
 14. The sore throat composition of claim 13, whereinthe auxillary agent is selected from the group consisting of lubricants,flavors, aromas, colorants, diluents, preservatives, glidants, andmixtures thereof.
 15. The sore throat composition of claim 13, in formof a lozenge or chewing gum.